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Molecular mechanisms of (-)-gossypol-induced apoptosis in human prostate cancer cells. Anticancer Res 2006 May-Jun;26(3A):1925-33

Date

07/11/2006

Pubmed ID

16827126

Scopus ID

2-s2.0-33745603202   46 Citations

Abstract

BACKGROUND: Gossypol, a natural compound present in cottonseeds, displays antiproliferative and pro-apoptotic effects against various cancer cells. The (-)-gossypol enantiomer is a more potent inhibitor of cancer cell growth. Here, the molecular mechanisms of apoptosis induced by (-)-gossypol were studied in human prostate cancer cells.

MATERIALS AND METHODS: After the prostate cancer cell DU-145 had been treated with (-)-gossypol, the trypan blue exclusion assay and DNA fragment end-labeling assay were used to stain the dead cells and to detect DNA laddering, respectively. The effects of (-)-gossypol on the expression of apoptotic-regulated gene markers in both death receptor- and mitochondria-mediated apoptotic pathways, such as the Bcl-2 family and caspase, etc., were detected by RT-PCR and Western blot analysis. To further investigate the apoptotic pathways induced by (-)-gossypol, different caspase inhibitors were used to block caspase activities and cell viability was detected by the CellTiter 96 AQueous assay in DU-145 cells.

RESULTS: At a 5-10 microM dose-level, (-)-gossypol significantly enhanced apoptosis measured by DNA fragmentation. (-)-Gossypol caused apoptosis in DU-145 cells through the down-regulation of Bcl-2 and Bcl-xL and the up-regulation of Bax at the mRNA and protein levels. (-)-Gossypol also activated caspases-3, -8 and -9 and increased PARP [poly (ADP-ribose) polymerase] cleavage. Furthermore, (-)-gossypol-induced apoptosis might be due to an increase in CAD (caspase-activated deoxyribonuclease) proteins and a decrease in ICAD (inhibitor of CAD) proteins. By using caspase inhibitors, (-)-gossypol caused apoptosis via the caspase-dependent pathways.

CONCLUSION: Our results indicated that the apoptotic processes caused by (-)-gossypol are mediated by the regulation of the Bcl-2 and caspase families in human prostate cancer cells. Our data also suggested that (-)-gossypol may have chemotheraputic benefits for prostate cancer patients.

Author List

Huang YW, Wang LS, Chang HL, Ye W, Dowd MK, Wan PJ, Lin YC

Authors

Yi-Wen Huang PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Li-Shu Wang PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Apoptosis
Caspases
Cell Line, Tumor
Enzyme Activation
Gossypol
Humans
Male
Poly(ADP-ribose) Polymerases
Prostatic Neoplasms
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger
jenkins-FCD Prod-406 0f9a74600e4e79798f8fa6f545ea115f3dd948b2